The cause of syphilis, Treponema pallidum, has never been cultivated in vitro. The inability to grow this spirochete in large numbers free from tissue has prevented successful studies leading to the development of a useful vaccine, studies on the mechanism of disease production, and the solution of complex immunologic problems associated with this disease. Previous studies from this laboratory have shown that this organism is capable of obtaining energy from glycolytic pathways, terminal electron transport to 02, and coupled oxidative phosphorylation. Additional enzymatic activities have been characterized. We now propose to obtain additional physiological information on its biosynthetic capabilities, transport problems, control mechanisms, and lytic phenomena, with the aim of applying such information to the in vitro axenic cultivation of this spirochete.